Polyphenol‑based interventions in breast cancer: Signaling pathways, molecular mechanisms and translational therapeutic strategies (Review)

Breast cancer (BC) comprises multiple molecular subtypes with distinct epidemiological, biological and therapeutic features. Although advances in diagnosis and systemic therapy have improved patient outcomes, therapeutic resistance, treatment‑related toxicity and disease recurrence remain major clinical challenges. Growing evidence suggests that plant‑derived polyphenols may influence BC progression through multiple biological mechanisms. These compounds can inhibit tumor‑cell proliferation, migration, angiogenesis, inflammation, epithelial‑mesenchymal transition and metastasis, while promoting apoptosis, autophagy, cell‑cycle arrest and tumor‑suppressive responses. Mechanistically, polyphenols may regulate several interconnected signaling pathways involved in BC development and progression, including PI3K/AKT/mTOR, p53, NF‑κB, STAT3, Wnt/β‑catenin and MAPK signaling. In addition to their direct effects on tumor cells, polyphenols may interact with the gut microbiome, which in turn influences polyphenol metabolism, estrogen homeostasis, immune regulation, inflammation and bioavailability. Probiotics, prebiotics and microbiota‑derived metabolites may further influence this polyphenol‑gut microbiome‑BC axis. Polyphenols have also been explored as adjuvant or supportive agents in combination with chemotherapy, endocrine therapy and radiotherapy, as well as in novel delivery systems designed to improve their bioavailability and therapeutic efficacy. However, most current evidence remains preclinical. Well‑designed clinical trials are therefore needed to define the optimal formulations, doses, safety profiles, pharmacokinetics and therapeutic relevance of polyphenol‑based interventions in BC.